Glycogen Synthase Kinase-3 in the Etiology and Treatment of Mood Disorders
The mood disorders major depressive disorder and bipolar disorder are prevalent, are inadequately treated, and little is known about their etiologies. A better understanding of the causes of mood disorders would benefit from improved animal models of mood disorders, which now rely on behavioral meas...
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Frontiers Research Foundation
2011
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3152743/ |
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pubmed-31527432011-08-31 Glycogen Synthase Kinase-3 in the Etiology and Treatment of Mood Disorders Jope, Richard Scott Neuroscience The mood disorders major depressive disorder and bipolar disorder are prevalent, are inadequately treated, and little is known about their etiologies. A better understanding of the causes of mood disorders would benefit from improved animal models of mood disorders, which now rely on behavioral measurements. This review considers the limitations in relating measures of rodent behaviors to mood disorders, and the evidence from behavioral assessments indicating that glycogen synthase kinase-3 (GSK3) dysregulation promotes mood disorders and is a potential target for treating mood disorders. The classical mood stabilizer lithium was identified by studying animal behaviors and later was discovered to be an inhibitor of GSK3. Several mood-relevant behavioral effects of lithium in rodents have been identified, and most have now been shown to be due to its inhibition of GSK3. An extensive variety of pharmacological and molecular approaches for manipulating GSK3 are discussed, the results of which strongly support the proposal that inhibition of GSK3 reduces both depression-like and manic-like behaviors. Studies in human postmortem brain and peripheral cells also have identified correlations between alterations in GSK3 and mood disorders. Evidence is reviewed that depression may be associated with impaired inhibitory control of GSK3, and mania by hyper-stimulation of GSK3. Taken together, these studies provide substantial support for the hypothesis that inhibition of GSK3 activity is therapeutic for mood disorders. Future research should identify the causes of dysregulated GSK3 in mood disorders and the actions of GSK3 that contribute to these diseases. Frontiers Research Foundation 2011-08-09 /pmc/articles/PMC3152743/ /pubmed/21886606 http://dx.doi.org/10.3389/fnmol.2011.00016 Text en Copyright © 2011 Jope. http://www.frontiersin.org/licenseagreement This is an open-access article subject to a non-exclusive license between the authors and Frontiers Media SA, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and other Frontiers conditions are complied with. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Jope, Richard Scott |
| spellingShingle |
Jope, Richard Scott Glycogen Synthase Kinase-3 in the Etiology and Treatment of Mood Disorders |
| author_facet |
Jope, Richard Scott |
| author_sort |
Jope, Richard Scott |
| title |
Glycogen Synthase Kinase-3 in the Etiology and Treatment of Mood Disorders |
| title_short |
Glycogen Synthase Kinase-3 in the Etiology and Treatment of Mood Disorders |
| title_full |
Glycogen Synthase Kinase-3 in the Etiology and Treatment of Mood Disorders |
| title_fullStr |
Glycogen Synthase Kinase-3 in the Etiology and Treatment of Mood Disorders |
| title_full_unstemmed |
Glycogen Synthase Kinase-3 in the Etiology and Treatment of Mood Disorders |
| title_sort |
glycogen synthase kinase-3 in the etiology and treatment of mood disorders |
| description |
The mood disorders major depressive disorder and bipolar disorder are prevalent, are inadequately treated, and little is known about their etiologies. A better understanding of the causes of mood disorders would benefit from improved animal models of mood disorders, which now rely on behavioral measurements. This review considers the limitations in relating measures of rodent behaviors to mood disorders, and the evidence from behavioral assessments indicating that glycogen synthase kinase-3 (GSK3) dysregulation promotes mood disorders and is a potential target for treating mood disorders. The classical mood stabilizer lithium was identified by studying animal behaviors and later was discovered to be an inhibitor of GSK3. Several mood-relevant behavioral effects of lithium in rodents have been identified, and most have now been shown to be due to its inhibition of GSK3. An extensive variety of pharmacological and molecular approaches for manipulating GSK3 are discussed, the results of which strongly support the proposal that inhibition of GSK3 reduces both depression-like and manic-like behaviors. Studies in human postmortem brain and peripheral cells also have identified correlations between alterations in GSK3 and mood disorders. Evidence is reviewed that depression may be associated with impaired inhibitory control of GSK3, and mania by hyper-stimulation of GSK3. Taken together, these studies provide substantial support for the hypothesis that inhibition of GSK3 activity is therapeutic for mood disorders. Future research should identify the causes of dysregulated GSK3 in mood disorders and the actions of GSK3 that contribute to these diseases. |
| publisher |
Frontiers Research Foundation |
| publishDate |
2011 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3152743/ |
| _version_ |
1611469873080172544 |